The Yale ADRC seeks to advance our understanding of Alzheimer's disease with the eventual goal of translating laboratory discoveries into novel effective clinical therapies. Five Cores (Administrative, Clinical, Data, Biomarker/Pathology and Outreach) and 3 Research Projects (Lysosomes, Post-Synaptic Densities and GABAergic Networks) will work together to achieve this goal. Our unifying theme is a focus on the cell biology of specific neurons, and its disruption in Alzheimer's disease triggered by abnormal forms of Amyloid-? peptide. Research Projects will focus on specific neuronal organelles and specific neuronal subtypes perturbed in disease and make use of human tissue analysis and human subject imaging to evaluate mechanistic hypotheses. The Biomarker/Pathology Core will develop novel, sensitive and high-throughput mass spectrometry assays by targeted multiple-reaction monitoring (MRM) to monitor disease mechanisms. A key emphasis will be the translational development of research findings into therapeutic benefit. To support the future strength of Alzheimer's research, the Yale ADRC will strive to advance the careers of Young Investigators through mentorship from a distinguished Internal Advisory Committee, and through Pilot Project awards. In addition to collecting clinical data and biospecimens of brain, CSF, DNA, serum, blood cells and iPSCs for analysis by members of the ADRC research team, the ADRC will support other Yale NIH-funded research studies on related topics and contribute materials to national NIA-sponsored research networks. The Outreach Core will connect with the community to provide greater knowledge regarding Alzheimer's disease and related dementia.